Understanding the genetics of atopic allergy, a common disorder in man, has obvious clinical implications for both the detection and treatment of allergic individuals. As detailed in this application, numerous measures of allergic response are now available for genetic and epidemiologic studies. This provides an excellent opprotunity for the testing and further development of analytical methods to differentiate between and characterize genetic and environmental factors involved in human immune response and disease susceptibility. The specific aims of this project are: 1) to investigate environmental factors affecting immune response (such as age, sex, exposure to allergens and smoking); 2) to analyze family dta for the presence of major genes determining total basal serum IgE levels, response to a given allergen and overall immune responsiveness; 3) to analyze family data with particular reference to HLA haplotypes to investigate the question of HLA-linked immune response genes; 4) to map any genetic loci involved in allergic response to a specific chromosomal region in man. Data collected from approximately 600 unrelated individuals and 43 local families (both parents and at least 4 children) and 73 Amish families (both parents and an average of 6 children) will be analyzed. Extensive interview data on medical history and exposure to allergens, results of skin-testing to a wide variety of substances including pollens, fungal spores and animal danders, total serum IgE levels and specific IgE and IgG antibody response towards ultra-pure components of grass and ragweed pollens are available on all individuals. Approximately 400 of the unrelated individuals have been typed for HLA-A,B,C,D and all family members are being typed for HLA-A,B,C,D and a wide variety of polymorphic genetic markers. Exising methodology can not be used for the analyses without modification. New statistical approaches are needed for a complete analysis of this extensive data base.